A Phase I, Randomised, Double Blind, Placebo Controlled, 3-part Study to Assess the Safety, Tolerability and Pharmacokinetics of Single and Multiple Inhaled Doses of RPL554 Administered by Nebuliser to Healthy Male Subjects and Stable COPD Subjects.

Brief Summary

Detailed Description

This is a randomised, double blind, placebo controlled study of a new suspension formulation of RPL554 comprising a Single Ascending Dose (SAD) phase (Part A) in healthy subjects, a Multiple Ascending Dose (MAD) phase (Part B) in healthy subjects and a MAD phase (Part C) in stable chronic obstructive pulmonary disease (COPD) subjects. Each cohort should comprise 10 subjects in a 7 active: 3 placebo ratio Subjects will be screened in the 14 days before the first dose of study drug and have an end of study visit 4 to 10 days after the last dose of study drug. Part A. Single Ascending Dose Study in Healthy Male Subjects aged 18-50. Each subject will receive a single dose of study drug. The starting dose will be 1.5 mg with planned escalation as 2 fold multiples unless the safety data indicates the escalation should be at smaller intervals. If RPL554 is not well tolerated at a particular dose level, the dose may be reduced for the next cohort.The decision on whether or not to escalate to each new dose level, and the dose, will be based on a formal review by the Dose Review Group (DRG). Part B. Multiple Ascending Dose Study in Healthy Male Subjects aged 18-50. The starting dose for Part B will be determined from the data in Part A of the study. Each subject will receive the following doses of study drug and will be confined to the study centre during dosing: three doses at intervals of 8 hours on Days 1 to 5, followed by a single morning dose on Day 6. The DRG may determine on the basis of safety or PK data that the dosing interval for subsequent cohorts will be every 12 hours, rather than every 8 hours. Part C. Multiple Ascending Dose in moderate, stable COPD Subjects aged 40-75 Subjects will have no known significant concurrent diseases, will not have had a recent exacerbation, and will be expected to be able to withhold regular bronchodilator therapy for the duration of the treatment phase of the study. Rescue medication with ipratropium will be allowed (and its use recorded) and subjects may continue inhaled corticosteroids at a stable dose. The dosing schedule will be the same as for Part B Dose Escalation Procedures The decision on whether or not to escalate to each new dose level and from one part of the study to the next and the selected dose will be based on a formal review by the DRG of safety data. The DRG will include the Principal Investigator and Sponsor's Medical Expert (and/or delegates) and will meet by teleconference to review safety data for each cohort. The DRG will review all available safety data (including adverse events \[AEs\], safety laboratory tests, spirometry and ECG data) collected up to 24 hours post dose for Part A, and for up to 24 hours post final dose for Parts B and C. Data collected during the study will be entered on case report forms and transferred to a database using double entry. Blinding will be maintained until all queries are resolved and the database is locked. AEs will be summarised by study treatment and further by intensity and relationship to study treatment. The study will primarily be evaluated using descriptive statistics. The sample size selected is not based on any formal power calculation.

Primary Outcomes

Secondary Outcomes

• Pharmacokinetics (trough measurement Blood sampling for RPL554 concentration)(24 hour profile after first and last dose, trough measurement on Days 2-5 for Parts B and C)